T cells are required for clearance of a bacterial infection with Bordetella pertussis (Leef et al. 2000, Wolfe et al. 2005). It appears that both arms of the adaptive immune response, respectively coordinated by TH1 and TH2 cells, play a role in bacterial clearance with vaccination. For example, it is indicated by investigations that whole cell vaccines induce a TH1 response while acellular vaccination induces a mixed TH1- TH2 response (Mills et al. 1998). Natural immune response to infection favors a TH1 response (Mills 2001).
Pertussis is composed of a number of antigens in the form of its bacterial toxins, many of which have immunomodulatory roles (Hou et al. 2003, Loucka et al. 2002, Ross et al. 2003, Ryan et al. 1998). Thus, cytokine secretion elicited by the various toxins directs the potentiation of the immune response to either TH1 or TH2 cells. Several experiments support the conclusion that the response to pertussis is mediated by TH1 and TH2 cells (Leef et al. 2000, Mills et al. 1993, Mills et al. 1998).
CD8+ cytotoxic T cells do not appear to play a significant role in bacterial clearance of pertussis. While immunization of mice lacking CD4+ T cells did not protect them from infection, immunization of CD8- mice did lead to protection (Leef et al. 2000). Thus, it appears that cytotoxic cell mediated immunity is not critical for the pertussis immune response. The potentiation of the cell mediated response is most likely due to effects of bacterial toxins such as pertussis toxin (PT), pertactin (PRN), filamentous hemagglutinin (FHA), and adenylate cyclase (CyaA). While PT increases the TH1 response, CyaA has been shown to synergize with lipopolysaccharide (LPS) to induce TH2 response (Ross et al. 2004, Ryan et al.1998). Signaling provided by LPS activation of dendritic cells increases IL-12, which favors a TH1 response through the activation of IFNγ secretion by NK cells (Higgins et al. 2003).
Profiles of the cytokine environment during an infection with Bordetella pertussis explain the polarization towards a TH1 response. After challenge with Bordetella pertussis, T cells are present in abundance. These T cells produced IFNγ, but not IL-4 or IL-10 (Leef et al. 2000). This cytokine pattern suggests these T cells are CD4+ TH1 cells. Another study found T cells that secreted IL-2 and IFNγ, but not IL-4 (Mills et al. 1993). Still another study cites IL-23 (a TH1-polarizing cytokine) as important in the pertussis response (Fedele et al. 2004). TH1 cells are responsible for the activation of macrophages. Also, they induce B cells to secrete opsonizing antibody (Janeway et al. 2005).
Other studies, however, point to the necessity of antibodies in clearance of pertussis as evidence that TH2 cells must play a role. Indeed, studies involving acellular (rather than whole-cell) vaccination produce an immune response with TH2 markers, such as IL-10 and IL-5 (Ohman et al. 2005). TH2 cells stimulate B cells to differentiate into antibody-secreting plasma cells (Janeway et al. 2005).
The polarization of an immune response towards TH1 or TH2 has profound effects upon the course of bacterial clearance. The former leads to cell-mediated immunity and IgG-led opsonization, whereas the latter results in neutralization of bacteria through humoral responses and IgM, IgA, and IgE (Janeway et al. 2005). There is ample evidence through both acellular and whole cell experiments to indicate that TH1 and TH2 cells coordinate a response that integrates humoral and cell-mediated branches of the adaptive immune response. This is further supported by the location of pathogen in both intracellular and extracellular locations in the respiratory tract (Mills et al. 1998). A reservoir of pathogen within macrophages requires TH1 stimulation, while bacterial neutralization (particularly by IgA) requires TH2 cells. Finally, TH1 may be further necessary for their induction of opsonizing functions by B cells (Mills et al. 1998).
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